Review Study Challenges Use of Antidepressants for Chronic Pain

Chronic pain — including pain that is not adequately explained by an underlying disease — spans a wide range of conditions.[1] It is common, can be debilitating and its treatment often is suboptimal. Some doctors prescribe antidepressants for adults suffering from chronic pain conditions, even when depression is not known to be associated with these conditions and even though the Food and Drug Administration has not approved most antidepressants for this use. Such inappropriate prescribing seems to be widespread, as a 2019 multinational population-based study observed that chronic pain is the most common potential reason for treatment among at least 41% of new users of antidepressants.[2]

A new review study shows limited evidence of low or moderate quality supporting the effectiveness of antidepressants for several pain conditions. This review was published in the Feb. 1, 2023, issue of The BMJ.

The new review study[3]

The researchers of the review study examined all systematic reviews — defined as peer-reviewed studies that used systematic methods to search the literature and synthesize data — that were published between 2012 and 2022 and compared the effectiveness of antidepressants with that of a placebo for treating any pain condition in adult patients. Overall, there were 26 reviews (encompassing 42 distinct comparisons) that collectively included 156 trials and enrolled over 25,000 patients. These systematic reviews covered 22 pain conditions; each condition had a single review except for fibromyalgia (which had five reviews), neuropathic pain and chronic tension headache (each of which had two reviews).

The systematic reviews studied several classes of antidepressants, mainly selective serotonin reuptake inhibitors (SSRIs; for example, fluoxetine [PROZAC] and paroxetine [PAXIL]), serotonin and norepinephrine reuptake inhibitors (SNRIs; for example, desvenlafaxine [PRISTIQ], duloxetine [CYMBALTA], milnacipran [SAVELLA] and venlafaxine [EFFEXOR XR]) and tricyclic antidepressants (for example, amitriptyline [generic only], desipramine [NORPRAMIN], doxepin [SILENOR] and nortriptyline [PAMELOR]).

None of the 42 comparisons in the systematic reviews reported high-certainty evidence about the effectiveness of antidepressants for any pain condition. In 31 comparisons, antidepressants were either not effective (five comparisons) or had inconclusive evidence of effectiveness (26 comparisons). Of the remaining comparisons, four suggested moderate-certainty evidence for the effectiveness of SNRIs for back pain, fibromyalgia, neuropathic pain and postoperative pain, and three other comparisons showed low-certainty evidence for the effectiveness of this antidepressant class, one comparison each for depression and comorbid chronic pain, knee osteoarthritis and pain associated with breast cancer treatment. Finally, low-certainty evidence was found in four effectiveness comparisons: SSRIs for depression and comorbid chronic pain and tricyclic antidepressants for pain associated with irritable bowel syndrome, neuropathic pain and chronic tension headache.

Even for the conditions for which antidepressants were moderately effective, it is unclear whether these effects result in meaningful clinical benefit. This is because the pain reductions due to antidepressants in these comparisons tended to be smaller than 10 points on a pain scale that ranges from zero to 100. In addition, the risk reduction of pain in patients taking SNRIs for fibromyalgia was small.

Another limitation is that nearly half of the clinical trials included in the reviews had ties to the pharmaceutical industry, a well-recognized source of bias. This was particularly a concern for the evidence on the effectiveness of SNRIs because 47 related clinical trials (68%) had industry ties.

The review did not include serious adverse effects because most of the included trials were not adequately powered to detect differences in these outcomes. Although the review examined safety and tolerability of antidepressants as secondary outcomes, most of the evidence for these outcomes was imprecise.

In conclusion, due to the limited effectiveness of antidepressants for chronic pain and uncertain evidence about their safety and tolerability, the use of antidepressants for chronic pain is not worthwhile.

What You Can Do

Do not take antidepressants to relieve chronic pain. If you are currently taking an antidepressant for this reason, do not stop this medication suddenly or without consulting your doctor, as withdrawal symptoms may occur.

Importantly, antidepressants may increase the risk of suicidal thoughts or actions. People who use these drugs and have thoughts of suicide should talk to their doctors or counselors promptly.

To manage noncancer pain, talk to your doctor about non-opioid drug options, such as acetaminophen (TYLENOL and generics) or ibuprofen (ADVIL, IBU-TAB, MIDOL LIQUID GELS, MOTRIN IB, TAB-PROFEN and generics).[4]

Do not take opioid medications for chronic pain — outside of active cancer treatment, palliative care or end-of-life care — unless the benefits of these medications clearly exceed their risks and you are under frequent care of a knowledgeable health care professional who has a plan for dose escalation and tapering of these medications.[5]

Keep in mind that although pain medications may be needed in some instances to manage chronic pain, they are not the only solution. When possible, it is best to use an individualized long-term program that includes nondrug options, such as lifestyle changes, exercise or physiotherapy.

Report all serious adverse events associated with the use of antidepressants or other medications to the FDA’s MedWatch adverse-event reporting program by visiting http://www.fda.gov/MedWatch or by calling 800-FDA-1088.
 

References

[1] Stannard C, Wilkinson C. Rethinking use of medicines for chronic pain. BMJ. 2023;380(February 1):170.

[2] Tamblyn R, Bates DW, Buckeridge DL, et al. Multinational comparison of new antidepressant use in older adults: a cohort study. BMJ Open. 2019;9(5):e027663.

[3] Ferreira GE, Abdel-Shaheed C, Underwood M, et al. Efficacy, safety, and tolerability of antidepressants for pain in adults: overview of systematic reviews. BMJ. 2023;380(February 1):e072415.

[4] Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain-United States, 2016. JAMA. 2016;315(15):1624-1645.

[5] Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain—United States, 2016. JAMA. 2016;315(15):1624-1645.